Drug-induced lung injury represents an increasingly frequent clinical problem. The diversity of suspected drugs and complicating variables associated with underlying disease state, prevents an adequate delineation of possible mechanisms of drug injury in a patient population. This study proposes to investigate nitrofurantoin and Bleomycin-inuced lung injury in animal models using a two-pronged approach: 1) an in vitro cytotoxicity assay to assess the direct injury of drugs to lung parenchumal cells, and 2) an in vivo model of drug injury, whereby bronchoalveolar lavage will monitor the inflammatory cell traffic of the lower respiratory tract. The in vitro assay using 51Cr labeled lung explants will isolate the two variables of primary concern, i.e., the drug and the lung parenchyma, in order to assess the direct effect of a drug on lung parenchymal cells. Various agents will be used to modulate the in vitro drug toxicity providing two major advantages: 1) it may clarify the drug's mechanism for injury (for example, antioxidants protecting the lung cells from a drug which generates oxygen radicals), and 2) it may assist in predicting which agents in vivo may reduce or exacerbate the drug-induced lung injury. The in vivo study will utilize bronchoalveolar lavage in drug-injured animals to assess the potential role for an inflammatory or immunologic response to mediate an indirect mechanism of lung tissue injury. The in vitro and in vivo approaches will be used in both animal models (the rate and the mouse). The rat will be utilized because prior in vitro studies of rats lung cells noted a close similarity to human lung cells in their response to oxidant injury. The mouse model will also be used because the immunopathology of the mouse has been better characterized than the rat, and future investigative tools, such as the use of specific antisera directed against lymphocyte subpopulations, are commercially available. The two animal models offer a complementary approach to the investigation of drug-induced injury with the potential for future investigation into possible mechanism of drug injury. The use of an animal model system permits easy manipulation of a variety of factors which might modulate the drug toxicity, and thus, will hopefully improve the understanding of drug-induced injury in man.